We are studying four major means by which accessory cells affect lymphocyte activation. 1) It has been observed that only IA/DR positive cells can successfully present activating agents to lymphocytes. We have established that human monocytes from cord blood or adult peripheral circulation can be induced to express DR antigens by "resting" lymphocytes or by immune interferon (IFNGamma). Conversely, monocytes lose their DR expression with in vitro culture or by incubation with prostaglandins or antibody to IFNGamma. Thus, this major histocompatibility product can be modulated in various ways which in turn provides a means of influencing lymphocyte reactivity. 2) Accessory cells are said to "process" stimulants. We established that paraformaldehyde-fixed human monocytes can activate T lymphocytes, provided they are preincubated with the stimulant for several hours at 37 degrees C and subsequently supplemented with IL-1. Furthermore, if the monocytes were exposed to lysosomotropic agents during the preincubation period and then fixed, they could no longer activate lymphocytes. This suggests that stimulant processing at the lysosomal level is necessary to enable the stimulant to interact with DR antigens and the T-lymphocyte receptor. 3) We have ascertained that several cell types in addition to monocytes that can act as accessory cells, can also produce IL-1: (a) a subset of DR-positive peripheral human large granular lymphocytes with natural killer activity, and (b) 7 or 10 EBV-transformed human B-cell lines tested. Although all the B-cell lines were DR positive, only those which produced an IL-1-like activity could function as accessory cells. This data leads to the hypothesis that any cell type that is capable of activating T cells, and hence initiating immune responses must be DR positive and an IL-1 secretor. 4) Finally, a cascade of cell-cytokine interactions serves to promote lymphocyte activation. IL-1 is known to induce the production of IL-2. We have shown that IL-2 in turn induces human IFNGamma which in turn induces monocyte DR expression and IL-1 production.